This study aimed to investigate the effect of multidimensional spiritual psychotherapy on anxiety, depression, and attitude towards self and god in bone cancer patients after amputation. Forty one cancer patients with a history of Below-The-Knee amputation were recruited in this quasi-experimental study. The design included pre-and post-tests in experimental and control groups. The experimental group received 15 sessions of multidimensional spiritual psychotherapy. Cattell Anxiety Inventory (CAI), Beck Anxiety Inventory (BAI), Beck's Depression Inventory (BDI), Religious Adherence Questionnaire (RAQ), and Self-concept-God concept questionnaire were administered for data collection. There was a significant difference between the control and experimental groups in terms of anxiety (P=0.0001), Depression (P=0.0001), God-image (P=0.035, F(1,38)=4.79), God-concept (P=0.006, F(1,38)=8.58), self-image (P=0.0001, F(1,38)=98.62), and self-concept (P=0.0001, F(1,38)=120.56), psychological evolution (P=0.0001, F(1,38)=19.36), and religious adherence (P=0.0001, F(1,38)=84.21). The results of the study indicated that the emphasis on spirituality and the implementation of spiritual care could improve the cancer amputated patients' well-being.